Discovery of highly immunogenic spleen-resident FCGR3^(+)CD103^(+)cDC1s differentiated by IL-33-primed ST2^(+)basophils  

作　　者：Myeong-Ho Kang JungHyub Hong Jinjoo Lee Min-Suk Cha Sangho Lee Hye-Young Kim Sang-Jun Ha Yong Taik Lim Yong-Soo Bae 

机构地区：[1]Department of Biological Sciences,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyeonggi-do 16419,Republic of Korea [2]Center for Immune Research on Non-Lymphoid Organs,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyounggi-do 16419,Republic of Korea [3]Laboratory of Mucosal Immunology,Department of Biomedical Sciences,Seoul National University College of Medicine,103 Daehak-ro,Jongno-gu,Seoul 03080,Republic of Korea [4]Institute of Allergy and Clinical Immunology,Seoul National University Medical Research Center,Seoul,Republic of Korea [5]Department of Biochemistry,College of Life Science and Biotechnology,Yonsei University,Seoul 03722,Republic of Korea [6]Department of Nano Engineering and School of Chemical Engineering,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon-si,Gyeonggi-do 16419,Republic of Korea.

出　　处：《Cellular & Molecular Immunology》2023年第7期820-834,共15页中国免疫学杂志（英文版）

基　　金：the National Research Foundation of Korea(SRC-2017R1A5A1014560). This work was supported by grants from the National Research Foundation of Korea(SRC-2017R1A5A1014560)。

摘　　要：Recombinant interleukin-33(IL-33)inhibits tumor growth,but the detailed immunological mechanism is still unknown.IL-33-mediated tumor suppression did not occur in Batf3^(−/−)mice,indicating that conventional type 1 dendritic cells(cDC1s)play a key role in IL-33-mediated antitumor immunity.A population of CD103^(+)cDC1s,which were barely detectable in the spleens of normal mice,increased significantly in the spleens of IL-33-treated mice.The newly emerged splenic CD103^(+)cDC1s were distinct from conventional splenic cDC1s based on their spleen residency,robust effector T-cell priming ability,and surface expression of FCGR3.DCs and DC precursors did not express Suppressor of Tumorigenicity 2(ST2).However,recombinant IL-33 induced spleen-resident FCGR3^(+)CD103^(+)cDC1s,which were found to be differentiated from DC precursors by bystander ST2+immune cells.Through immune cell fractionation and depletion assays,we found that IL-33-primed ST2^(+)basophils play a crucial role in the development of FCGR3^(+)CD103^(+)cDC1s by secreting IL-33-driven extrinsic factors.Recombinant GM-CSF also induced the population of CD103^(+)cDC1s,but the population neither expressed FCGR3 nor induced any discernable antitumor immunity.The population of FCGR3^(+)CD103^(+)cDC1s was also generated in vitro culture of Flt3L-mediated bone marrow-derived DCs(FL-BMDCs)when IL-33 was added in a pre-DC stage of culture.FL-BMDCs generated in the presence of IL-33(FL-33-DCs)offered more potent tumor immunotherapy than control Flt3L-BMDCs(FL-DCs).Human monocyte-derived DCs were also more immunogenic when exposed to IL-33-induced factors.Our findings suggest that recombinant IL-33 or an IL-33-mediated DC vaccine could be an attractive protocol for better tumor immunotherapy.

关 键 词：Recombinant interleukin-33(IL-33) Highly immunogenic Spleen residency FCGR3^(+)CD103^(+)cDC1s ST2^(+)basophils Antitumor immunity 

分 类 号：R392[医药卫生—免疫学]